β-escin mitigates neuroinflammation and apoptosis caused by ischemic stroke through the inhibition of the interleukin-6/Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway

β-七叶皂苷通过抑制白细胞介素-6/Janus激酶2/信号转导及转录激活因子3信号通路,减轻缺血性卒中引起的神经炎症和细胞凋亡。

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Abstract

ObjectiveThis study aimed to investigate the protective effects of β-escin against neuroinflammatory injury and its influence on the interleukin-6/Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in a rat model of ischemic stroke.MethodsRats underwent a 2-h middle cerebral artery occlusion and were categorized into sham, middle cerebral artery occlusion, and middle cerebral artery occlusion treated with β-escin (0.45, 0.90, and 1.80 mg/kg) groups. Cerebral damage was assessed using 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining; neuronal apoptosis was evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay; serum levels of inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and interleukin-1β) were measured using enzyme-linked immunosorbent assay, and protein expression of the interleukin-6/Janus kinase 2/signal transducer and activator of transcription 3 pathway was analyzed using western blot.Resultsβ-escin administration dose-dependently reduced Longa scores, cerebral infarction volume, and pathological damage while also attenuating neuronal apoptosis. It significantly suppressed the release of proinflammatory cytokines and downregulated the expression of interleuin-6 and interleukin-6 receptor as well as the ratios of phosphorylated Janus Kinase 2/Janus Kinase 2 and phosphorylated signal transducer and activator of transcription 3/ signal transducer and activator of transcription 3. These protective effects were positively correlated with the dosage of β-escin.ConclusionThe findings suggested that β-escin exerted neuroprotective effects in ischemic stroke by modulating the interleukin-6/Janus kinase 2/signal transducer and activator of transcription 3 pathway, thereby reducing neuroinflammation and apoptosis.

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